The high mortality rate from TB is an urgent health issue. Globally, there were an estimated 9.27 million incident cases of TB in 2007, according to World Health Organization (WHO) data. This is an increase from 9.24 million cases in 2006, 8.3 million cases in 2000, and 6.6 million cases in 1990. Most of the estimated total cases in 2007 were in Asia (55%) and Africa (31%), with a small proportion in the Eastern Mediterranean (6%), Europe (5%), and the Americas (3%). The five top countries in terms of total incidence in 2007 were India (2.0 million), China (1.3 million), Indonesia (0.53 million), Nigeria (0.46 million), and South Africa (0.46 million). Of the 9.27 million incident cases, an estimated 1.37 million (15%) were HIV-positive; 79% of these HIV-positive cases were in the Africa and 11% were in South-East Asia.
Although the total number of incident cases of TB is increasing in absolute terms as a result of population growth, the number of cases per capita is falling. The rate of decline is slow, at less than 1% per year. Globally, rates peaked at 142 cases per 100,000 population in 2004. In 2007, there were an estimated 139 incident cases per 100,000 population. Incidence rates are falling in five of the six WHO regions (the exception is Europe, where rates are approximately stable).
There were an estimated 0.5 million cases of multidrug-resistant TB (MDR-TB). There are 27 countries (of which 15 are in Europe) that account for 85% of all such cases. The most prominent countries in terms of total numbers of MDR-TB cases are India (131,000), China (112,000), Russia (43,000), South Africa (16,000), and Bangladesh (15,000). By the end of 2008, 55 countries and territories had reported at least one case of extensively drug-resistant TB (XDR-TB) [World Health organization (WHO) Report 2009 [Guidelines for surveillance of drug resistance in tuberculosis. 4th Ed. WHO/HTM/TB/2009.422, WHO Press, Geneva, CH].
Remarkable achievements in TB control are associated with drug treatments. There have already been a large number of such TB medications. The first chemical preparations (streptomycin, sodium para-aminosalicylate, and tibon) appeared at the end of 1940s. Then ftivazide, isoniazid, and new effective chemical preparations such as ethionamide, canamycin, florimycin, cycloserine, and prothionamide were developed, allowing the most appropriate and effective individual treatment. Then rifampicin, ethambutol, and mycobutin, which are very effective TB drugs, became available. However, Mycobacterium tuberculosis with extensive resistance to these new drugs then emerged.
In standard TB therapy (for all forms of TB), the basic and most effective TB drugs are isoniazid (isonicotinic acid hydrazide, INH) [M. D. Mashkovsky: Pharma Products, vol. 2, Kharkov, Torsing, 1997, p. 332-333, 341-342.], a forerunner of this new development, and rifampicin [M. D. Mashkovsky: Pharma Products, vol. 2, Kharkov, Torsing, 1997, p. 332-333, 341-342; A. G. Khomenko: Chemotherapy of Pulmonary Tuberculosis, Moscow: Meditsina, 1980, 279 p.]. Although isoniazid shows a good therapeutic effectiveness, it is very toxic (LD50 is 150 mg/kg), and its long-term administration is associated with digestive, renal, emotional, hematological, and allergic disorders and toxic hepatitis. The main disadvantage of isoniazid is that resistance in M. tuberculosis is rapidly developed in 70% of patients and up to 30% of TB patients become chronic carriers. The semisynthetic antibiotic rifampicin is also very active against M. tuberculosis, although it has high toxic effects. As with isoniazid, the main disadvantage of rifampicin is a rapid development of rifampicin resistance in M. tuberculosis, which is observed in 40-50% of TB patients and significantly decreases the drug's effectiveness. In cases of rifampicin-resistant TB, it is necessary to combine rifampicin with other TB drugs (streptomycin, isoniazid, ethambutol, etc.) [M. D. Mashkovsky: Pharma Products, vol. 2, Kharkov, Torsing, 1997, p. 332-333, 341-342]. Resistance of M. tuberculosis to available TB drugs necessitated the development of new types of treatment and their combination.
The object of the new preparation outlined here is to prepare a new highly effective TB treatment that has minimal toxic effects and is stable during storage.